ClinVar Miner

Submissions for variant NM_000088.3(COL1A1):c.3479G>A (p.Gly1160Asp) (rs886039726)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000254780 SCV000322675 pathogenic not provided 2016-08-18 criteria provided, single submitter clinical testing A novel G1160D pathogenic variant was identified in the COL1A1 gene. It has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. G1160D occurs in the triple helical domain and replaces the Glycine in the canonical Gly-X-Y repeat. Mutations in these Glycines result in poor winding of the collagen triple helix and a less functional protein. The G1160D variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G1160D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby Glycine residues (G1151S/V, G1154R, G1157D, G1166C, G1169C/S) have been reported in the Human Gene Mutation Database in association with osteogenesis imperfecta (Stenson et al., 2014), supporting the functional importance of this region of the protein.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000254780 SCV000603112 likely pathogenic not provided 2017-05-01 criteria provided, single submitter clinical testing The p.Gly1160Asp variant has not been reported in the medical literature nor has it been previously identified by our laboratory. It has been reported to ClinVar (Variation ID 265680). The p.Gly1160Asp variant is absent from general population databases such as 1000 Genomes, NHLBI GO Exome Sequencing Project (ESP) , the Exome Aggregation Consortium (ExAC) browser and the Genome Aggregation Database (gnomAD) browser. This variant disrupts the repeating Gly-X-Y sequence motif of the collagen triple helix and is predicted to impair collagen function (Ben Amor 2011). Altogether, the p.Gly1160Asp variant has been classified as likely pathogenic.

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